Muscle patches obtained from induced pluripotent stem cells can help repair injuries as well as heart failure, according to a recent publication in Nature magazine.
This procedure has been carried out on a 46-year-old woman who is participating in a clinical trial. This person, who suffered a heart attack in 2016, which caused heart failure, had 10 patches of 400 million cells implanted on the surface of her heart through surgery. This way, her condition was stabilized for three months, and she was finally able to receive a heart transplant.
When her old heart was examined, it was found that the implanted patches were in place and had developed blood vessels. Previous studies had been carried out on Rhesus macaques in which patches containing between 40 and 200 million cells were tested. Ingo Kutschka, a cardiac surgeon at the University Medical Center Göttingen in Germany and co-author of the paper, said: “We now have, for the first time, a laboratory-grown biological transplant available that has the potential to stabilise and strengthen the heart muscle.” Jianyi Zhang said: “This is a breakthrough.” Professor Zhang specialises in bioengineering and specifically in the use of induced pluripotent stem cells, which are somatic cells reprogrammed to a quasi-embryonic state and subsequently differentiated into the required cell type.
This treatment is not intended to replace a full transplant. However, patients suffering from advanced heart failure who are waiting for a heart could receive significant help. The reality is that “less than 1% of patients who need one receive a heart transplant,” said Wolfram-Hubertus Zimmermann, a pharmacologist and co-author of the paper, who also added: this approach “offers another treatment to patients currently receiving palliative care.”
Fifteen people have participated in this trial so far, receiving muscle patches. The importance of this work is understood when we know that about 60 million people in the world suffer from heart failure and, of those with severe cases, more than half die within a year. On the other hand, there are not enough donors to cover this need and artificial pumping devices require an invasive surgical procedure and are expensive.
For a long time, attempts have been made to alleviate this type of ailment by implanting or directly injecting stem cells, or muscles derived from them, into the heart. However, this has produced immunological rejection, tumors or arrhythmias. Now, researchers from Zimmermann’s team worked with induced pluripotent cells and, from them, obtained cardiac muscle and connective tissue. These cells were embedded in a collagen hydrogel. Later, using a minimally invasive procedure, they were placed on the outside of the heart.
The patches were implanted in six macaques with heart failure and compared to a control group that was not treated. To prevent an immune response, the treated animals were given drugs. After six months, the primates that had received five patches had an increase in the thickness of the heart wall of up to 6 millimeters. In three of the macaques, there was a ten percent increase in the amount of blood pumped with each heartbeat. “This indicates that while the heart is pumping, the patches are contributing, and this then translates into an improvement in the pumping of the entire heart,” Zimmermann said. No arrhythmias or tumors occurred in any of the apes.
The patient who took part in the clinical trial suffered from severe heart failure and was awaiting a transplant. The medical team placed 10 muscle patches (4 by 9 centimeters) on the heart, applying a few stitches. To do this, he had to make an incision on the left side of the woman’s chest, and she was given two immunosuppressive drugs commonly used in transplants.
When examining the original heart after the transplant, the scientists observed that the areas where the implanted cells were located were intertwined with small blood vessels and were therefore supplied with nutrients and oxygen. “It is now clear that muscle can be added to a failing heart and that we can do so without safety concerns,” Zimmermann said. In the current follow-up trial, 20 patches have been implanted in each of the 15 participants. Currently, the researchers are testing new patch designs in macaques with the aim of minimising immunosuppressants.
Although the work is still in the early stages, the scientists plan to move on to phase III in view of the positive results obtained in terms of safety. On the other hand, it is worth noting that the patches have been obtained from the reprogramming of blood cells from a donor that have given rise to induced pluripotent stem cells (iPSC) and, from these, cardiomyocytes.
iPSCs were discovered by researcher S. Yamanaka in 2006, and their origin is ethically impeccable, avoiding the need to use embryonic stem cells. If these experiments go ahead, the suffering of many people around the world who are affected by these cardiac pathologies could be alleviated. In any case, we will have to wait for subsequent trials with a large number of participants to confirm the safety and efficacy of the treatment.
